Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma.

Tsitsiou, Eleni, Williams, Andrew Evan, Moschos, Sterghios, Patel, Ketan, Rossios, Christos, Jiang, Xiaoying, Adams, Oona-Delpuech, Macedo, Patricia, Booton, Richard, Gibeon, David, Chung, Kian Fan and Lindsay, Mark (2012) Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma. Journal of Allergy and Clinical Immunology, 129 (1). pp. 95-103. ISSN 0091-6749

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Official URL: http://dx.doi.org/10.1016/j.jaci.2011.08.011

Abstract

BACKGROUND

Although previous studies have implicated tissue CD4(+) T cells in the development and maintenance of the inflammatory response in asthmatic patients, little is known about the role of CD8(+) T cells. There is now accumulating evidence that microRNAs and other noncoding RNAs are important regulators of T-cell function.

OBJECTIVES

We sought to use transcriptomics to determine the activation state of circulating CD4(+) and CD8(+) T cells in patients with nonsevere and severe asthma.

METHODS

mRNA and noncoding RNA expression in circulating T cells was measured by means of microarray, quantitative real-time PCR, or both.

RESULTS

Comparison of mRNA expression showed widespread changes in the circulating CD8(+) but not CD4(+) T cells from patients with severe asthma. No changes were observed in the CD4(+) and CD8(+) T cells in patients with nonsevere asthma versus those in healthy control subjects. Bioinformatics analysis showed that the changes in CD8(+) T-cell mRNA expression were associated with multiple pathways involved in T-cell activation. As with mRNAs, we also observed widespread changes in expression of noncoding RNA species, including natural antisense, pseudogenes, intronic long noncoding RNAs (lncRNAs), and intergenic lncRNAs in CD8(+) T cells from patients with severe asthma. Measurement of the microRNA expression profile showed selective downregulation of miR-28-5p in CD8(+) T cells and reduction of miR-146a and miR-146b in both CD4(+) and CD8(+) T cells.

CONCLUSIONS

Severe asthma is associated with the activation of circulating CD8(+) T cells but not CD4(+) T cells. This response is correlated with the downregulation of miR-146a/b and miR-28-5p, as well as changes in the expression of multiple species of lncRNA that might regulate CD8(+) T-cell function.

Item Type: Article
Uncontrolled Keywords: Severe asthma, transcriptome, long noncoding RNA, microRNA
Subjects: A300 Clinical Medicine
B200 Pharmacology, Toxicology and Pharmacy
Department: Faculties > Health and Life Sciences > School of Life Sciences > Applied Sciences
Depositing User: Sterghios Moschos
Date Deposited: 24 Oct 2016 13:55
Last Modified: 24 Oct 2016 13:55
URI: http://nrl.northumbria.ac.uk/id/eprint/28137

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